Multiple layer article with interactive reinforcements linear ribbon fiber reinforcement for composite forms

Abstract

A method and composition are provided to treat traumatic brain injury and inhibit the cascade of secondary injury neuronal damage in a patient following traumatic brain injury. The method and composition are especially advantageous for immediate treatment at the situs of the traumatic brain injury. The method includes treating the traumatic brain injury by administering at least one effective dose of a peptidomimetic calpain inhibitor to the upper one-third of the patients nasal cavity, thereby enabling the at least one effective dose of peptidomimetic calpain inhibitor to bypass the patients blood-brain barrier and delivering the at least one effective dose of peptidomimetic calpain inhibitor to the patients central nervous system. The composition includes at least one effective dose of a peptidomimetic calpain inhibitor having a synthetic peptide of SEQ ID NOS: 2, 3, 5, 6, 7, 8, 9, or 10.

1 . A method of inhibiting neuronal damage in a patient following traumatic brain injury comprising:
 administering at least one effective dose of a peptidomimetic calpain inhibitor to the upper one-third of the patient's nasal cavity, thereby enabling the at least one effective dose of peptidomimetic calpain inhibitor to bypass the patient's blood-brain barrier and delivering the at least one effective dose of peptidomimetic calpain inhibitor to the patient's central nervous system; and   treating the traumatic brain injury.   
     
     
         2 . The method of  claim 1  wherein the at least one effective dose of peptidomimetic calpain inhibitor is administered to the upper one-third of the patient's nasal cavity as at least one of a liquid spray, a powdered spray, nose drops, a gel, an ointment, or a combination thereof. 
     
     
         3 . The method of  claim 1  wherein the peptidomimetic calpain inhibitor is a drug comprising a synthetic peptide of SEQ ID NOS: 2, 3, 5, 6, 7, 8, 9, or 10 and a pharmaceutically acceptable excipient or other additive selected from the group consisting of a hydrophobic blood-brain-barrier or a membrane-permeant amino acid sequence linked by a polyethylene glycol linker to the N-terminus of said peptide, SEQ ID NO. 11, SEQ ID NO. 12, a nonaqueous vehicle, nanoparticle encapsulation, a solvent, a diluent, adjuvant, a chelating agent, a stability enhancing additive, antimicrobial preservatives, antioxidants, buffers, an antibacterial or an antifungal agent, parabens, chlorobutanol, phenol, sorbic acid, an isotonic agent, a sugar, sodium chloride, a prolonged absorption agent, aluminum monostearate, a gelatin, or a combination thereof. 
     
     
         4 . The method of  claim 3  wherein the synthetic peptide is that of SEQ ID NO: 5. 
     
     
         5 . The method of  claim 3  wherein the synthetic peptide is that of SEQ ID NO: 2 or SEQ ID NO: 5 wherein the peptidic bond(s) of one or more of the following amino acid pairs in the sequence is replaced with a non-peptidic reduced amide bond: Ser4-Ser5, Tyr6-Ile7, Lys13-Arg14, Glu15-Val16, Lys21-Tyr22, Tyr22-Arg23. 
     
     
         6 . The method of  claim 3  wherein the synthetic peptide is that of SEQ ID NO: 2, wherein there is side-chain cyclization between Lys21 and Glu24. 
     
     
         7 . The method of  claim 1  wherein the at least one effective dose of peptidomimetic calpain inhibitor is 0.0001 to 1.0 mg/kg. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1  further comprising administering the at least one effective dose of peptidomimetic calpain inhibitor until the concentration of peptidomimetic calpain inhibitor in the patient's brain is within the range of 0.1 nM to 50 μM. 
     
     
         11 . The method of  claim 1  wherein the administration of the at least one effective dose of peptidomimetic calpain inhibitor treats neurodegeneration or inhibits memory loss or treats physical impairment or treats behavioral impairment in the patient, wherein the neurodegeneration is caused by the traumatic brain injury. 
     
     
         12 - 14 . (canceled) 
     
     
         15 . The method of  claim 1  wherein the traumatic brain injury is caused by a head injury. 
     
     
         16 . A traumatic brain injury induced neuronal damage inhibiting neurotherapeutic composition comprising:
 at least one effective dose of a peptidomimetic calpain inhibitor having a synthetic peptide of SEQ ID NOS: 2, 3, 5, 6, 7, 8, 9, or 10.   
     
     
         17 . The composition of  claim 16  further comprising a pharmaceutically acceptable excipient or other additive, said pharmaceutically acceptable excipient or other additive being at least one of a liquid spray, a powdered spray, nose drops, a gel, an ointment, or a combination thereof. 
     
     
         18 . The composition of  claim 17  wherein the pharmaceutically acceptable excipient or other additive is selected from the group consisting of a hydrophobic blood-brain-barrier or a membrane-permeant amino acid sequence linked by a polyethylene glycol linker to the N-terminus of said peptide, SEQ ID NO. 11, SEQ ID NO. 12, a nonaqueous vehicle, nanoparticle encapsulation, a solvent, a diluent, adjuvant, a chelating agent, a stability enhancing additive, antimicrobial preservatives, antioxidants, buffers, an antibacterial or an antifungal \agent, parabens, chlorobutanol, phenol, sorbic acid, an isotonic agent, a sugar, sodium chloride, a prolonged absorption agent, aluminum monostearate, a gelatin, or a combination thereof. 
     
     
         19 . The composition of  claim 16  wherein the synthetic peptide is that of SEQ ID NO: 5. 
     
     
         20 . The composition of  claim 16  wherein the synthetic peptide is that of SEQ ID NO: 2 or SEQ ID NO: 5 and wherein the peptidic bond(s) of one or more of the following amino acid pairs in the sequence is replaced with a non-peptidic reduced amide bond: Ser4-Ser5, Tyr6-Ile7, Lys13-Arg14, Glu15-Val16, Lys21-Tyr22, Tyr22-Arg23. 
     
     
         21 . The composition of  claim 16  wherein the synthetic peptide is that of SEQ ID NO: 2, wherein there is side-chain cyclization between Lys21 and Glu24. 
     
     
         22 . The composition of  18   claim 16  wherein the at least one effective dose of peptidomimetic calpain inhibitor is 0.0001 to 1.0 mg/kg. 
     
     
         23 . (canceled) 
     
     
         24 . The composition of  claim 16  further comprising the at least one effective dose of peptidomimetic calpain inhibitor having a volume of 0.015 to 1.0 ml. 
     
     
         25 - 28 . (canceled)